PROJECT SUMMARY Approximately 30% of the population will meet criteria for an alcohol use disorder (AUD) in their lifetime, making it the most prevalent substance use disorder in the United States. Posttraumatic stress disorder (PTSD), a condition characterized by symptoms of re-experiencing, avoidance, and hyper-arousal following a traumatic exposure, is present in approximately 6-8% of the general population, and has high comorbidity with AUD. Additionally, individuals with a family history of AUD have a disproportionately high rate of trauma exposure and both subsequent PTSD and AUD as compared with the general population, which suggests that other factors, including genetic, social environmental, and neurocognitive influences, may increase the risk for trauma exposure, posttraumatic stress disorder, and co-occurring AUD. However, no study to our knowledge has examined the influence of these factors together, using multiple assessments prospectively measured throughout adolescence and young adulthood. We hypothesize that trauma-exposed adolescents and young adults with a family history of AUD will have a higher risk for later PTSD and/or comorbid AUD than trauma- exposed subjects without a family history of AUD, and that these individuals will show less efficient cognitive functioning (i.e., response inhibition). In addition, we hypothesize that genetic risk variants influencing cognitive function may also influence risk for PTSD and/or AUD. We will address these hypotheses through the following Specific Aims: 1) examine the interaction of trauma exposure and family history of AUD on risk for PTSD and comorbid AUD across adolescence and young adulthood; 2) examine the interaction of family history of AUD and trauma exposure on neurocognitive function and behavior during a response inhibition task across adolescence and young adulthood; and 3) examine if genetic risk variants influencing neurocognitive function also influence PTSD and/or AUD risk. Data from the Collaborative Study on the Genetics of Alcoholism (COGA) prospective study (N=3,812) at two-year intervals (baseline and 3 follow-ups) will be utilized to conduct longitudinal analyses assessing differences in DSM-IV PTSD symptoms/diagnosis, alcohol dependence symptoms/diagnosis, and neurocognitive functioning. Genetic variants meeting significance criteria in the Cognitive Genomics Consortium's recently published genome-wide association study (N=35,298) will be tested for association with risk for PTS and comorbid AUD. Findings from this research proposal could inform early intervention and treatment strategies aimed at reducing the severity and endurance of PTSD and AUD.